1. Field of the Invention
The present invention relates to the treatment of various forms of sleep disordered breathing, and, more particularly, to treating sleep disordered breathing with an adaptive, state-dependent positive airway pressure system.
2. Description of the Related Art
Sleep disordered breathing (SDB) is a common condition with important clinical consequences for affected individuals. Physicians and other experts have suggested that SDB exists as a continuum between a pure central apnea (caused by a lost drive to breathe) and a pure obstructive apnea (due to mechanics of the upper airway). Obstructive sleep apnea (OSA) is characterized by repetitive collapse of the upper airway during sleep as a result of lost compensation during sleep for an anatomic deficiency. This yields episodes of reduced airflow, hypoxemia (reduced oxygen level in the blood), hypercapnia (elevated circulating carbon dioxide, CO2), and arousal from sleep to reestablish a stable airway. However, emerging data suggest that the pathophysiology of SDB is not limited to just collapse of the upper airway.
Respiration is the process where O2-rich, CO2-defficient air is brought into the lungs with diaphragm and/or thoracic muscle contraction so that CO2 in the deoxygenated, CO2-rich blood returning to the lungs can passively follow its concentration gradient and diffuse from the blood into the alveoli and O2 can follow its concentration gradient from the alveoli into the blood. Respiration is regulated by negative feedback. The primary variable controlled by this system is CO2 in the bloodstream, measured as the partial pressure of carbon dioxide, PCO2. An increase in PCO2 at central and peripheral chemoreceptors leads to a compensatory increase in ventilation (i.e., ventilation is used to rid the body of CO2) and a decrease in PCO2 at the chemoreceptors leads to a decrease in ventilation. In this way, PCO2 is maintained within a physiological range by controlling ventilation. If the negative feedback of this system is compromised, then for a given ventilatory disturbance (e.g., increased ventilation with an arousal from sleep), the resulting ventilatory response may be amplified instead of damped. This can lead to episodes of hyperventilation followed by central apnea (a form of SDB that may have little to do with upper airway collapsibility).
The respiratory control system can be modeled as a system of compartments (brain compartment, lung compartment, etc.) interconnected by the vasculature. Carbon dioxide flows via the bloodstream between these compartments. The plant compartment describes the input-output relationship between ventilation and the PCO2 in the lungs and consists of two sub-compartments, the lungs and the body tissues. The plant can be described by a system of nonlinear first order differential equations, but can be simplified using the concept of plant gain, which represents the change in alveolar partial pressure of carbon dioxide PACO2 over the change in ventilation (ΔPACO2/Δventilation). Under room air conditions, the plant gain determines the decrease in PACO2 (thereby increasing the CO2 concentration gradient between the blood and alveoli) for a given increase in ventilation. Thus, limiting the decrease in PACO2 (i.e. decreasing the CO2 concentration gradient) with ventilation by increasing the concentration of CO2 in the alveoli lowers the gain of the plant compartment. Because the overall gain of ventilatory control is a product of all of the compartment gains, lowering the plant gain reduces the loop gain of the entire system and helps to dampen the response to a given disturbance.
Numerous studies have demonstrated that positive airway pressure administered with a patient interface, such as a mask, can effectively treat OSA when titrated to the appropriate pressure, and, in most cases, will also improve sleep architecture. Data also suggest there are significant clinical benefits to treating OSA. However, there are reasons to believe that poor adherence to therapy (i.e., ongoing time spent asleep at the prescribed continuous positive airway pressure (CPAP) is less than target) and significant residual SDB during therapy may have negative consequences regarding clinical outcomes.
Cheyne-Stokes respiration (CSR) is another form of sleep disordered breathing observed in some individuals with increased sensitivity to chemical respiratory stimuli. It is usually associated with heart failure, but may also be a comorbidity of some neurological conditions. FIG. 1 illustrates a typical Cheyne-Stokes respiration (CSR) pattern 30, which is characterized by rhythmic waxing periods 32 and waning periods 34 of respiration, with regularly recurring periods of high respiratory drive (hyperpnea) 36 and low respiratory drive (hypopnea or apnea) 38. A typical Cheyne-Stokes cycle, generally indicated at 40 in FIG. 1, lasts about one minute and is characterized by a crescendo (arrow A), in which the peak respiratory flow of the patient increases over several breath cycles, and decrescendo (arrow B) variation in peak flow, in which the peak respiratory flow of the patient decreases over several breath cycles. The disruption in sleep, as well as the periodic desaturation of arterial oxygen (PO2), stresses the cardio-vascular system and specifically the heart. Hyperpnea often causes arousals and, thus, degrades sleep quality.
Emerging data suggest that an adaptive algorithm that can provide non-invasive mechanical ventilation when central apneas are detected and support ventilation when the instantaneous peak airflow falls below an adaptive threshold can significantly reduce or even eliminate CSR by augmenting ventilation during a state of low respiratory drive.
Others have shown in independent studies that CSR can be significantly reduced and even eliminated in the laboratory with inhaled CO2 or added dead space to promote rebreathing of CO2 (i.e., interventions to reduce the plant gain). FIG. 2, from Lorenzi-Filho G., Rankin F., Bies I., Bradley T. D.; Effects of Inhaled Carbon Dioxide and Oxygen of Cheyne-Stokes Respiration in Patients with Heart Failure, American Journal of Respiratory and Critical Care Medicine 1999; 159:1490-1498, hereby incorporated by reference in its entirety, shows the elimination of CSR and central apneas by inhalation of CO2 (sample B) compared to the breathing of air (sample A). As shown in FIG. 2, various measurements were taken in the study to show the effects of CO2 and O2 inhalation including electroencephalogram (EEG), submental electromyogram (EMG), tidal volume (VT), saturation of oxygen (SaO2), fraction of end tidal carbon dioxide (FETCO2), and transcutaneous partial pressure of carbon dioxide (PtcCO2).
There has also been success in treating CSR in a small outpatient-based, intention-to-treat trial of low-flow CPAP that promotes rebreathing of CO2. U.S. Pat. No. 6,752,150 to Remmers et al. (“the '150 patent”), which is hereby incorporated by reference in its entirety, discloses a modified continuous positive airway pressure (CPAP) system designed to promote rebreathing of CO2 to treat central apneas. Furthermore, the benefit of improving ventilatory control may be generalized beyond those with CSR or central apneas. Individuals with obstructive sleep apnea (OSA) that demonstrate CPAP emergent central apneas appear to have issues with both upper airway collapsibility and ventilatory control. Thus, stabilizing the upper airway with positive airway pressure and decreasing the plant gain by increasing the concentration of alveolar CO2 during episodes of hyperventilation may improve the efficacy of positive pressure therapy in these individuals. In individuals with a stable upper airway, an intervention to decrease the plant gain may be adequate without the use of positive airway pressure.
U.S. patent application Ser. No. 10/716,360 (Publication No. US 2004/0144383 A1) (“the '360 application”), which is hereby incorporated by reference in its entirety, discloses a system and method for treating sleep disordered breathing by providing precise concentrations of CO2 and O2 to the patient in conjunction with positive airway pressure. A supplemental source of CO2 is provided and mixed with a supply of O2 before being supplied to the patient. This configuration thus addresses the sleep disordered breathing problems relating to upper airway obstruction as well as abnormal control of breathing (e.g., CSR) since it maintains the positive airway pressure flow.
Bi-level positive airway pressure therapy is a form of positive airway pressure therapy that has been advanced in the treatment of sleep apnea and other breathing and cardiac disorders. In bi-level therapy, pressure is applied to the airway of a patient alternately at relatively higher and lower pressure levels so that the therapeutic pressure is alternately administered at a larger and smaller magnitude force. The higher and lower magnitude positive prescription pressure levels are known as inspiratory positive airway pressure (IPAP) and expiratory positive airway pressure (EPAP), and are synchronized with the patient's inspiratory cycle and expiratory cycle, respectively.
An adaptive form of bi-level therapy, known as variable positive airway pressure (VarPAP), is disclosed in U.S. Pat. No. 6,752,151 to Hill (“the '151 patent”), which is hereby incorporated by reference in its entirety. The VarPAP system implements many of the standard functions of a positive airway pressure support device, as well as an algorithm that adjusts IPAP, EPAP, or both in order to counter a CSR pattern. A flow sensor is utilized to determine the patient's peak flow during respiratory cycles, which allows a controller to monitor the peak flows to determine whether the patient is experiencing CSR other sleep disordered breathing. The algorithm involves a three-layer process, each occurring at different time intervals, in order to continually adapt the supplied gas pressure to suit the patient's needs and to detect any occurrences of sleep disorders. In the event of a hypopnea or apnea period, known as central apneas as described above, the VarPAP according to the disclosed system may provide a “machine breath” in order to stimulate respiration in the patient.
Another disclosure, pending U.S. application Ser. No. 11/235,520 (Publication No. US 2006/0070624) (“the '520 application”), which is hereby incorporated by reference in its entirety, aims to improve upon the '151 patent and makes determinations based on the parameters of instantaneous average inspiratory flow and maximum average inspiratory flow. These averaged parameters serve to smooth out or filter the direct instantaneous parameters used in the '151 patent and may therefore lead to smoother results. Further improvements are made relating to the monitoring of intra-breath flow and enhanced disorder detection.